A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21

被引：649

作者：

Tomlinson, Ian ^{[1
]}

Webb, Emily

Carvajal-Carmona, Luis

Broderick, Peter

Kemp, Zoe

Spain, Sarah

Penegar, Steven

Chandler, Ian

Gorman, Maggie

Wood, Wendy

Barclay, Ella

Lubbe, Steven

Martin, Lynn

Sellick, Gabrielle

Jaeger, Emma

Hubner, Richard

Wild, Ruth

Rowan, Andrew

Fielding, Sarah

Howarth, Kimberley

Silver, Andrew

Atkin, Wendy

Muir, Kenneth

Logan, Richard

Kerr, David

Johnstone, Elaine

Sieber, Oliver

Gray, Richard

Thomas, Huw

Peto, Julian

Cazier, Baptiste

Houlston, Richard

机构：

[1] Canc Res UK, Mol & Populat Genet Lab, London WC2A 3PX, England

[2] Univ London, Queen Mary Coll, Barts & London Med Sch, Inst Canc, London WC1E 7HU, England

[3] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England

[4] St Marks Hosp, Canc Res UK, Colorectal Canc Unit, Harrow HA1 3UJ, Middx, England

[5] Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Queens Med Ctr, Nottingham NG7 2UH, England

[6] Univ Oxford, Radcliffe Infirm, Dept Clin Pharmacol, Oxford OX2 6HA, England

[7] Univ Oxford, Canc & Immunogenet Lab, Weatherall Inst Mol Med, Oxford OX3 9DS, England

[8] Univ Birmingham, Birmingham Clin Trials Unit, Birmingham B15 2RR, W Midlands, England

[9] St Marks Hosp, Canc Res UK, Family Canc Clin, Harrow HA1 3UJ, Middx, England

[10] Univ London London Sch Hyg & Trop Med, Non Communicable Dis Epidemiol Unit, London WC1E 7HT, England

[11] Inst Canc Res, Epidemiol Sect, Sutton SM2 5NG, Surrey, England

来源：

NATURE GENETICS | 2007年 / 39卷 / 08期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/ng2085

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Much of the variation in inherited risk of colorectal cancer (CRC) is probably due to combinations of common low risk variants. We conducted a genome- wide association study of 550,000 tag SNPs in 930 familial colorectal tumor cases and 960 controls. The most strongly associated SNP (P = 1.72 x 10(-7), allelic test) was rs6983267 at 8q24.21. To validate this finding, we genotyped rs6983267 in three additional CRC case-control series (4,361 affected individuals and 3,752 controls; 1,901 affected individuals and 1,079 controls; 1,072 affected individuals and 415 controls) and replicated the association, providing P = 1.27 x 10(-14) (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16-1.39) and 1.47 (95% c.i.: 1.34-1.62) for heterozygotes and rare homozygotes, respectively. Analyses based on 1,477 individuals with colorectal adenoma and 2,136 controls suggest that susceptibility to CRC is mediated through development of adenomas (OR = 1.21, 95% c.i.: 1.10-1.34; P = 6.89 x 10(-5)). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia.

引用

页码：984 / 988

页数：5

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